Digital Commons Network^™

An Assessment Of Pediatric Residency Applicant Perceptions Of "Fit" During The Virtual Interview Era, Jason D. Vadhan, Jorge G. Zarate Rodriguez, Michael Wallendorf, Michael M. Awad, Andrew J. White

2020-Current year OA Pubs

PURPOSE: Residency recruitment events and interviews are widely considered an integral component of the residency match experience. Due to the COVID-19 pandemic, residency recruitment and interviewing throughout the 2020-2021 academic year were performed virtually, which created challenges for applicants' ability to discern "fit" to a program. Given this change, it is reasonable to suspect that applicants would be less able to discern program fit. Therefore, this study evaluated how virtual interviews impacted pediatric residency applicants' ability to assess factors contributing to fit and subsequently how applicants assessed their self-perceived fit to their top-ranked programs.

METHODS: An online, anonymous survey was …

Better Operating Room Ventilation As Determined By A Novel Ventilation Index Is Associated With Lower Rates Of Surgical Site Infections, Bernard Surial, Andrew Atkinson, Rüdiger Külpmann, Arnold Brunner, Kurt Hildebrand, Benoît Sicre, Nicolas Troillet, Andreas Widmer, Eveline Rolli, Judith Maag, Jonas Marschall

2020-Current year OA Pubs

OBJECTIVE: The aim was to assess the impact of operating room (OR) ventilation quality on surgical site infections (SSIs) using a novel ventilation index.

BACKGROUND: Previous studies compared laminar air flow with conventional ventilation, thereby ignoring many parameters that influence air flow properties.

METHODS: In this cohort study, we surveyed hospitals participating in the Swiss SSI surveillance and calculated a ventilation index for their ORs, with higher values reflecting less turbulent air displacement. For procedures captured between January 2017 and December 2019, we studied the association between ventilation index and SSI rates using linear regression (hospital-level analysis) and with the …

American Cochlear Implant Alliance Task Force Guidelines For Clinical Assessment And Management Of Adult Cochlear Implantation For Single-Sided Deafness, Margaret T. Dillon, Armine Kocharyan, Ghazal S. Daher, Matthew L. Carlson, William H. Shapiro, Hillary A. Snapp, Jill B. Firszt

2020-Current year OA Pubs

The indications for cochlear implantation have expanded to include individuals with profound sensorineural hearing loss in the impaired ear and normal hearing (NH) in the contralateral ear, known as single-sided deafness (SSD). There are additional considerations for the clinical assessment and management of adult cochlear implant candidates and recipients with SSD as compared to conventional cochlear implant candidates with bilateral moderate to profound sensorineural hearing loss. The present report reviews the current evidence relevant to the assessment and management of adults with SSD. A systematic review was also conducted on published studies that investigated outcomes of cochlear implant use on …

A Randomized Phase Ii Study Of Sm-88 Plus Methoxsalen, Phenytoin, And Sirolimus In Patients With Metastatic Pancreatic Cancer Treated In The Second Line And Beyond, Marcus S Noel, Semmie Kim, Marion L Hartley, Steve Wong, Vincent J Picozzi, Harry Staszewski, Dae Won Kim, Jan M Van Tornout, Philip Agop Philip, Vincent Chung, Allyson J Ocean, Andrea Wang-Gillam

2020-Current year OA Pubs

BACKGROUND: This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1).

RESULTS: Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor …

Real-World Utilization And Outcomes Of Systemic Therapy Among Patients With Advanced Or Recurrent Endometrial Cancer In The United States, Jinan Liu, Bruno Emond, Eric M Maiese, Marie-Hélène Lafeuille, Patrick Lefebvre, Isabelle Ghelerter, Caterina Wu, Jean A Hurteau, Premal H Thaker

2020-Current year OA Pubs

OBJECTIVE: Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States.

METHODS: This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004-31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line …

Quantitative Tumor Depth Determination Using Dual Wavelength Excitation Fluorescence, Christine M. O'Brien, Kevin W. Bishop, Haini Zhang, Xiao Xu, Leo Shmuylovich, Elizabeth Conley, Karen Nwosu, Kathleen Duncan, Suman B. Mondal, Gail Sudlow

2020-Current year OA Pubs

No abstract provided.

Associations Between Transcranial Doppler Vasospasm And Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study, Abhijit V. Lele, Rafael Wabl, Sarah Wahlster, Jade Keen, Andrew M. Walters, Christine T. Fong, Vasu B. Dhulipala, Umeshkumar Athiraman, Anne Moore, Monica S. Vavilala, Louis J. Kim, Michael R. Levitt

2020-Current year OA Pubs

OBJECTIVE: The objective is to examine the relationship between transcranial Doppler cerebral vasospasm (TCD-vasospasm), and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH).

METHODS: In a retrospective cohort study, using univariate and multivariate analysis, we examined the association between TCD-vasospasm (defined as Lindegaard ratio >3) and patient's ability to ambulate without assistance, the need for tracheostomy and gastrostomy tube placement, and the likelihood of being discharged home from the hospital.

RESULTS: We studied 346 patients with aSAH; median age 55 years (Interquartile range IQR 46,64), median Hunt and Hess 3 [IQR 1-5]. Overall, 68.6% (n=238) had TCD-vasospasm, and 28% (n=97) had …

Brain-Wide Versus Genome-Wide Vulnerability Biomarkers For Severe Mental Illnesses, Peter Kochunov, Aris Sotiras, Et Al.

2020-Current year OA Pubs

Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual's brain-wide similarity to the expected SMI patterns derived from meta-analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual's similarity to genome-wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 …

Manufacturing-Dependent Change In Biological Activity Of The Tlr4 Agonist Gsk1795091 And Implications For Lipid A Analog Development, Neeltje Steeghs, Haeseong Park, Et Al.

2020-Current year OA Pubs

A phase I trial (NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll-like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti-OX40 monoclonal antibody], GSK3359609 [anti-ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. The primary endpoint was safety; other endpoints included efficacy, pharmacokinetics, and pharmacodynamics (PD). Manufacturing of GSK1795091 formulation was modified during the trial to streamline production and administration, resulting in reduced PD (cytokine) activity. Fifty-four patients received GSK1795091 with a combination partner; 32 received only the modified GSK1795091 formulation, 15 received only the original formulation, and seven switched mid-study from the original to …

Facial Paresis As The First Sign In Atypical Facioscapulohumeral Muscular Dystrophy, Nneoma S. Wamkpah, John J. Chi

2020-Current year OA Pubs

No abstract provided.

A Phase I First-In-Human Study Of Abbv-383, A B-Cell Maturation Antigen × Cd3 Bispecific T-Cell Redirecting Antibody, In Patients With Relapsed/Refractory Multiple Myeloma, Anita D'Souza, Ravi Vij, Et Al.

2020-Current year OA Pubs

PURPOSE: ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study.

METHODS: Patients with RRMM (≥ three prior lines including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody) were eligible. ABBV-383 was administered intravenously over 1-2 hours once every 3 weeks, without any step dosing. A 3 + 3 design with backfilling for dose escalation was used (intrapatient escalation to highest …

Loneliness, Social Isolation, And Social Support In Older Adults With Active Cancer During The Covid-19 Pandemic, Katherine Clifton, Feng Gao, Joann Jabbari, Mary Van Aman, Patricia Dulle, Janice Hanson, Tanya M Wildes

2020-Current year OA Pubs

INTRODUCTION: The COVID-19 pandemic has had a considerable impact on mental health. The social distancing and stay-at-home orders have likely also impacted loneliness, social isolation, and social support. Older adults, particularly those with comorbidities such as cancer, have a greater potential to be impacted. Here we assessed loneliness, social isolation, and social support in older adults undergoing active cancer treatment during the pandemic.

MATERIALS AND METHODS: A mixed methods study in which quantitative data and qualitative response items were collected in parallel was conducted in 100 older adults with cancer. Participants completed a survey by telephone with a series of …

N-Terminal Acetylation And Arginylation Of Actin Determines The Architecture And Assembly Rate Of Linear And Branched Actin Networks, Samantha M Chin, Tomoyuki Hatano, Lavanya Sivashanmugam, Andrejus Suchenko, Anna S Kashina, Mohan K Balasubramanian, Silvia Jansen

2020-Current year OA Pubs

The great diversity in actin network architectures and dynamics is exploited by cells to drive fundamental biological processes, including cell migration, endocytosis, and cell division. While it is known that this versatility is the result of the many actin-remodeling activities of actin-binding proteins, such as Arp2/3 and cofilin, recent work also implicates posttranslational acetylation or arginylation of the actin N terminus itself as an equally important regulatory mechanism. However, the molecular mechanisms by which acetylation and arginylation alter the properties of actin are not well understood. Here, we directly compare how processing and modification of the N terminus of actin …

Peroxisomal Regulation Of Energy Homeostasis: Effect On Obesity And Related Metabolic Disorders, Brian Kleiboeker, Irfan J Lodhi

2020-Current year OA Pubs

BACKGROUND: Peroxisomes are single membrane-bound organelles named for their role in hydrogen peroxide production and catabolism. However, their cellular functions extend well beyond reactive oxygen species (ROS) metabolism and include fatty acid oxidation of unique substrates that cannot be catabolized in mitochondria, and synthesis of ether lipids and bile acids. Metabolic functions of peroxisomes involve crosstalk with other organelles, including mitochondria, endoplasmic reticulum, lipid droplets and lysosomes. Emerging studies suggest that peroxisomes are important regulators of energy homeostasis and that disruption of peroxisomal functions influences the risk for obesity and the associated metabolic disorders, including type 2 diabetes and hepatic …

Amyloid-Β And Tau Deposition Influences Cognitive And Functional Decline In Down Syndrome, Monika Grigorova, Beau Ances, Et Al.

2020-Current year OA Pubs

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [

Acute-Onset, Painful, Acral Granuloma Annulare In A 52-Year-Old Female, Faisal S Ahmad, Michael R Vittori, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.

Durable Melanoma Control Following Disseminated Talimogene Laherparepvec Herpetic Infection, Leonid Shmuylovich, Aubriana M Mcevoy, Ryan C Fields, Leonel Hernandez-Aya, George Ansstas, David Y Chen

2020-Current year OA Pubs

No abstract provided.

Implementation Of Telemedicine Infectious Diseases Consultation In A Rural Hospital Using The Active Implementation Framework, Jason P Burnham, Stephanie A Fritz, Graham A Colditz

2020-Current year OA Pubs

In this pilot study, guided by the Active Implementation Framework, telemedicine infectious diseases consultation was provided to hospitalized inpatients at a rural Missouri hospital. Measured outcomes included the implementation outcomes of feasibility, acceptability, appropriateness, and fidelity, as well as clinical outcomes of readmissions and death.

Human Immunodeficiency Virus Pre-Exposure Prophylaxis Knowledge, Attitudes, And Self-Efficacy Among Family Planning Providers In The Southern United States: Bridging The Gap In Provider Training, Aditi Ramakrishnan, Jessica M Sales, Micah Mccumber, Leah Powell, Anandi N Sheth

2020-Current year OA Pubs

BACKGROUND: Pre-exposure prophylaxis (PrEP) is an effective human immunodeficiency virus (HIV) prevention intervention, but its access and use are suboptimal, especially for women. Healthcare providers provision of PrEP is a key component of the

METHODS: We used data from providers in clinics that did not currently provide PrEP from a web-based survey administered to Title X clinic staff in 18 Southern states from February to June 2018. We developed generalized linear mixed models to evaluate associations between provider-, clinic-, and county-level variables with provider knowledge, attitudes, and self-efficacy in PrEP care, guided by the Consolidated Framework for Implementation Research.

RESULTS: …

Hospital Trajectories And Early Predictors Of Clinical Outcomes Differ Between Sars-Cov-2 And Influenza Pneumonia, Patrick G Lyons, Aaloke Mody, Alice Bewley, Katherine Dittman, Aisling Doyle, Samuel L Windham, Tej M Patel, Bharat Neelam Raju, Matthew Keller, Andrew P Michelson, Thomas Kannampallil, Elvin H Geng, Pratik Sinha, Et Al.

2020-Current year OA Pubs

BACKGROUND: A comparison of pneumonias due to SARS-CoV-2 and influenza, in terms of clinical course and predictors of outcomes, might inform prognosis and resource management. We aimed to compare clinical course and outcome predictors in SARS-CoV-2 and influenza pneumonia using multi-state modelling and supervised machine learning on clinical data among hospitalised patients.

METHODS: This multicenter retrospective cohort study of patients hospitalised with SARS-CoV-2 (March-December 2020) or influenza (Jan 2015-March 2020) pneumonia had the composite of hospital mortality and hospice discharge as the primary outcome. Multi-state models compared differences in oxygenation/ventilatory utilisation between pneumonias longitudinally throughout hospitalisation. Differences in predictors of …

Implementation Of An Electronic, Secure, Web-Based Application To Support Routine Hand Hygiene Observation With Immediate Direct Feedback And Anonymized Benchmarking, Simon Simonet, Jonas Marschall, Rolf Kuhn, Matthias Schlegel, Christian R Kahlert

2020-Current year OA Pubs

A secure web-based electronic tool was developed and implemented to record adherence to hand hygiene during routine care and to provide direct feedback including anonymized benchmarking. It was found suitable for documenting hand hygiene improvements in a local campaign and following rollout to other institutions in 2013, the tool is currently used in >100 hospitals in Switzerland and will play a major part in upcoming national hand hygiene campaigns.

International Consensus Guidelines For Adjuvant Radiation Therapy For Bladder Cancer After Radical Cystectomy: Update From An Ibis Workgroup, Flor Verghote, Paul Sargos, John P Christodouleas, Vedang Murthy, Brian C Baumann, Piet Dirix, Charlien Berghen, Leen Paelinck, Tom Vercauteren, Valérie Fonteyne

2020-Current year OA Pubs

PURPOSE: In 2016, international consensus clinical target volume (CTV) guidelines for adjuvant radiation treatment after radical cystectomy in patients with muscle-invasive bladder cancer with high risk for locoregional failure (LRF) were published. A subsequent external validation study recommended several CTV optimizations (CTV-OPT). This study aimed to update international consensus guidelines based on new clinical experiences.

METHODS AND MATERIALS: Phase 1 (delineation interobserver variability): Four observers delineated the CTV of 9 patients post radical cystectomy, as in clinical practice. Interobserver agreement in contouring was evaluated using volume- and κ-statistics. Phase 2 (pattern of failure analysis): Among a prospective cohort of 72 …

A Report Of 2 Cases Of The Use Of The Inari Flowtriever System In The Treatment Of Pulmonary Embolism, Richard Pham, Alexander Sasha Ushinsky, Naganathan Mani, Pavan K Kavali

2020-Current year OA Pubs

The FlowTriever System (Inari Medical, Irvine, California) is the first FDA-approved mechanical thrombectomy device used for treatment of pulmonary embolism. This device enables nonsurgical removal of pulmonary blood clots without the use of thrombolytic medication and its associated risks. We report 2 cases of successful application of the Inari FlowTriever in treatment of pulmonary embolism and right atrial thrombus.

The Programmed Death-1 Signaling Axis Modulates Inflammation And Lv Structure/Function In A Stress-Induced Cardiomyopathy Model, Tomohiro Hayashi, Sajal K Tiwary, Kory J Lavine, Sandeep Acharya, Michael Brent, Luigi Adamo, Attila Kovacs, Douglas L Mann

2020-Current year OA Pubs

The role of immune checkpoints in the setting of tissue injury remains unknown. Using an experimental model of isoproterenol (ISO)-induced stress cardiomyopathy, we show that ISO-induced myocardial injury provokes tissue-autonomous up-regulation of the programmed death-1 (PD-1):programmed death ligand (PD-L) axis in cardiac resident innate immune cells and T cells. PD-1 signaling was responsible for modulating the acute inflammatory response, as well as normalization of impaired left ventricular structure and function after ISO injection. Necrotic cardiac extracts were sufficient to increase the expression of PD-1 in macrophages and T cells in vitro. Viewed together these studies suggest that the PD-1:PD-L signaling …

Infectious Complications Of Abortion, L. Lewis Wall, Awol Yemane

2020-Current year OA Pubs

This article reviews the infectious complications of abortion (both spontaneous and induced) and the management of this condition. The key points are: (1) Making abortion illegal does not reduce its incidence or prevalence; rather, it only makes abortions unsafe, increasing the likelihood of infectious complications. (2) Timely recognition of developing sepsis in the pregnant patient is critical. This requires constant vigilance and a high index of suspicion. (3) Rapid intravenous administration of broad-spectrum antibiotics targeted to the likely intrauterine source of infection as soon as sepsis is diagnosed is critical to prevent severe sepsis, septic shock, and multisystem organ failure. …

Self-Care Management Of Bothersome Symptoms As Recommended By Clinicians For Patients With A Chronic Condition: A Delphi Study, Heleen Westland, Shayleigh Dickson Page, Michelle Van Rijn, Subhash Aryal, Kenneth E Freedland, Christopher Lee, Anna Strömberg, Ercole Vellone, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel

2020-Current year OA Pubs

BACKGROUND: Chronically medically ill patients often need clinical assistance with symptom management, as well as self-care interventions that can help to reduce the impact of bothersome symptoms. Experienced clinicians can help to guide the development of more effective self-care interventions.

OBJECTIVE: To create a consensus-based list of common bothersome symptoms of chronic conditions and of self-care management behaviors recommended to patients by clinicians to reduce the impact of these symptoms.

METHODS: A two-round Delphi study was performed among an international panel of 47 clinicians using online surveys to identify common and bothersome symptoms and related self-care management behaviors recommended to …

Engineering Diverse Fatty Acid Compositions Of Phospholipids In Escherichia Coli, Wenqin Bai, Winston E Anthony, Christopher J Hartline, Shaojie Wang, Bin Wang, Jie Ning, Fong-Fu Hsu, Gautam Dantas, Fuzhong Zhang

2020-Current year OA Pubs

Bacterial fatty acids (FAs) are an essential component of the cellular membrane and are an important source of renewable chemicals as they can be converted to fatty alcohols, esters, ketones, and alkanes, and used as biofuels, detergents, lubricants, and commodity chemicals. Most prior FA bioconversions have been performed on the carboxylic acid group. Modification of the FA hydrocarbon chain could substantially expand the structural and functional diversity of FA-derived products. Additionally, the effects of such modified FAs on the growth and metabolic state of their producing cells are not well understood. Here we engineer novel Escherichia coli phospholipid biosynthetic pathways, …

Guidance For The Diagnosis And Treatment Of Hypolipidemia Disorders, Cindy Bredefeld, Nicholas O Davidson, Et Al.

2020-Current year OA Pubs

The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol …

Local Failure Events In Prostate Cancer Treated With Radiotherapy: A Pooled Analysis Of 18 Randomized Trials From The Meta-Analysis Of Randomized Trials In Cancer Of The Prostate Consortium (Leviathan), Ting Martin Ma, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

CONTEXT: The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear.

OBJECTIVE: To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT.

EVIDENCE ACQUISITION: A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival …

Covariance-Based Vs. Correlation-Based Functional Connectivity Dissociates Healthy Aging From Alzheimer Disease, Jeremy F. Strain, Matthew R. Brier, Aaron Tanenbaum, Brian A. Gordon, John E. Mccarthy, Aylin Dincer, Daniel S. Marcus, Richard J. Perrin, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances, Abraham Z. Snyder, Et Al.

2020-Current year OA Pubs

Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched …